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GAD-Alum (Diamyd) Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes (DIAGNODE-1) (DIAGNODE)

Primary Purpose

Diabetes Mellitus, Type 1

Status
Completed
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
GAD-Alum
Vitamin D
Sponsored by
Johnny Ludvigsson
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring Diamyd, Diabetes, Juvenile Diabetes, Diabetes Type 1, Type 1 Diabetes, Autoimmune Diabetes, Insulin Dependent Diabetes, Type 1 Diabetes Mellitus, rhGAD65 (Recombinant Human GAD with molecular mass 65,000), GAD65, GAD-Alum, Diabetes Mellitus, Diabetes mellitus Type 1, Glucose Metabolism Disorders, Metabolic Diseases, Vitamin D

Eligibility Criteria

12 Years - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Informed consent given by patients
  2. Type 1 diabetes according to the ADA (American Diabetes Association) classification with < 6 months diabetes duration
  3. Age 12.00-29.99 years at diagnosis of Type 1 diabetes
  4. Fasting C-peptide ≥0.12 nmol/L
  5. Pos GADA(Antibodies to GAD with molecular mass 65,000) but < 50 000 random units
  6. Females must agree to avoid pregnancy and have a negative urine pregnancy test
  7. Patients of childbearing potential must agree to using adequate contraception, until 1 year after the last administration of GAD-Alum.

Exclusion Criteria:

  1. Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted)
  2. Continuous treatment with any inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted)
  3. Treatment with any oral or injected anti-diabetic medications other than insulin
  4. Treatment with Vitamin D, marketed or not, or unwilling to abstain from such medication during the trial
  5. A history of anaemia or significantly abnormal haematology results at screening
  6. A history of epilepsy, head trauma or cerebro-vascular accident, or clinical features of continuous motor unit activity in proximal muscles
  7. Clinically significant history of acute reaction to vaccines or other drugs in the past
  8. Treatment with any vaccine, including influenza vaccine, within 4 months prior to planned first study drug dose or planned treatment with any vaccine up to 4 months after the last injection with study drug.
  9. Participation in other clinical trials with a new chemical entity within the previous 3 months
  10. Inability or unwillingness to comply with the provisions of this protocol
  11. A history of alcohol or drug abuse
  12. A significant illness other than diabetes within 2 weeks prior to first dosing
  13. Known human immunodeficiency virus (HIV) or hepatitis
  14. Females who are lactating or pregnant (the possibility of pregnancy must be excluded by urine βHCG (beta-human chorionic gonadotropin) on-site within 24 hours prior to the GAD-Alum treatment)
  15. Males or females not willing to use adequate contraception until 1 year after the last GAD-Alum treatment
  16. Presence of associated serious disease or condition, including active skin infections that preclude subcutaneous injection, which in the opinion of the investigator makes the patient non-eligible for the study
  17. Deemed by the investigator not being able to follow instructions and/or follow the study protocol

Sites / Locations

  • Linköping University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GAD-Alum+Vitamin D

Arm Description

GAD-Alum (Diamyd) injected into Lymph Nodes Dosage and interval: One injection of 4 µg Diamyd will be administered into the lymph nodes at three occasions, with one month intervals Vitamin D (Calciferol) in oral solution. Dosage and interval: 2000 IU daily for 120 days

Outcomes

Primary Outcome Measures

Number of Subjects With Injection Site Reactions Month 1
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Number of Subjects With Injection Site Reactions Month 2
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Number of Subjects With Injection Site Reactions Month 3
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Number of Subjects With Injection Site Reactions Month 32
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)

Secondary Outcome Measures

Mean Change in C-peptide AUC (Area Under the Curve) (Mean 120min) Value, Month 15
Change from baseline to month 15 in C-peptide AUC (Area Under the Curve) (mean 120min) value AUC (mean 120min) (nmol/L) is the C-peptide AUC during an MMTT (nmol/L*minutes) divided by the duration of the MMTT (minutes) i.e. C-peptide weighted average concentration
Mean Change in C-peptide AUC(Mean 120min) Value, Month 30
Change from baseline to month 30 in C-peptide AUC(mean 120min) value AUC (mean 120min) (nmol/L) is the C-peptide AUC during an MMTT (nmol/L*minutes) divided by the duration of the MMTT (minutes) i.e. C-peptide weighted average concentration
Mean Change in C-peptide AUC(Mean 120min) Value, Month 43
Change from baseline to month 43 in C-peptide AUC(mean 120min) value AUC (mean 120min) (nmol/L) is the C-peptide AUC during an MMTT (nmol/L*minutes) divided by the duration of the MMTT (minutes) i.e. C-peptide weighted average concentration
Mean Change in C-peptide 90-minute Value, Month 15
Change from baseline to month 15 in C-peptide 90-minute value
Mean Change in C-peptide 90-minute Value, Month 30
Change from baseline to month 30 in C-peptide 90-minute value
Mean Change in C-peptide 90-minute Value, Month 43
Change from baseline to month 43 in C-peptide 90-minute value
Mean Change in Fasting C-peptide Value, Month 15
Change from baseline to month 15 in fasting C-peptide value
Mean Change in Fasting C-peptide Value, Month 30
Change from baseline to month 30 in fasting C-peptide value
Mean Change in Fasting C-peptide Value, Month 43
Change from baseline to month 43 in fasting C-peptide value
Mean Change in HbA1c, Month 15
Change from baseline to month 15 in HbA1c
Mean Change in HbA1c, Month 30
Change from baseline to month 30 in HbA1c
Mean Change in HbA1c, Month 43
Change from baseline to month 43 in HbA1c
External Insulin Dose, Baseline
External insulin dose at baseline
External Insulin Dose, Month 15
External insulin dose at month 15
External Insulin Dose, Month 30
External insulin dose at month 30
External Insulin Dose, Month 43
External insulin dose at month 43
Mean IDAA1c Values, Baseline
Insulin dose-adjusted HbA1c (IDAA1c)
Mean IDAA1c Values, Month 15
Insulin dose-adjusted HbA1c (IDAA1c)
Mean IDAA1c Values, Month 30
Insulin dose-adjusted HbA1c (IDAA1c)
Mean IDAA1c Values, Month 43
Insulin dose-adjusted HbA1c (IDAA1c)

Full Information

First Posted
December 9, 2014
Last Updated
April 15, 2020
Sponsor
Johnny Ludvigsson
Collaborators
Swedish Child Diabetes Foundation, Ostergotland County Council, Sweden, Diamyd Medical AB
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1. Study Identification

Unique Protocol Identification Number
NCT02352974
Brief Title
GAD-Alum (Diamyd) Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes (DIAGNODE-1)
Acronym
DIAGNODE
Official Title
Open Label Pilot Trial in Adults With Recent-onset T1D to Evaluate the Safety, Diabetes Status and Immune Response of GAD-antigen (Diamyd®) Therapy Administered Into Lymph Nodes in Combination With an Oral Vitamin D Regimen
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
January 2015 (undefined)
Primary Completion Date
October 2019 (Actual)
Study Completion Date
October 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Johnny Ludvigsson
Collaborators
Swedish Child Diabetes Foundation, Ostergotland County Council, Sweden, Diamyd Medical AB

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The objectives of the main study is to: Evaluate the safety of giving GAD-Alum (Glutamic acid decarboxylase) (Diamyd) directly into lymph glands in combination with an oral vitamin D regimen Evaluate how the above mentioned treatments influence the immune system and endogenous insulin secretion. The objective of the sub-study is to: Evaluate safety after a fourth injection with 4 μg GAD-Alum direct into an inguinal lymph gland in 3 adult patients from the main study Evaluate how the above mentioned treatment influences the immune system and endogenous insulin secretion.
Detailed Description
Eligible patients will be treated with 4 µg GAD-Alum into an inguinal lymph gland at three occasions, with one month intervals in combination with Vitamin D (14 000 IU/week) for 4 months, starting 1 month prior to first GAD-Alum injection. A sub-study will include three adult patients from the main study and evaluate safety after a fourth injection with 4 μg GAD-Alum into an inguinal lymph gland in combination with oral vitamin D intake. The Prolonged Extension Study Period is 12 months and will start 30,5 months after baseline.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
Keywords
Diamyd, Diabetes, Juvenile Diabetes, Diabetes Type 1, Type 1 Diabetes, Autoimmune Diabetes, Insulin Dependent Diabetes, Type 1 Diabetes Mellitus, rhGAD65 (Recombinant Human GAD with molecular mass 65,000), GAD65, GAD-Alum, Diabetes Mellitus, Diabetes mellitus Type 1, Glucose Metabolism Disorders, Metabolic Diseases, Vitamin D

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GAD-Alum+Vitamin D
Arm Type
Experimental
Arm Description
GAD-Alum (Diamyd) injected into Lymph Nodes Dosage and interval: One injection of 4 µg Diamyd will be administered into the lymph nodes at three occasions, with one month intervals Vitamin D (Calciferol) in oral solution. Dosage and interval: 2000 IU daily for 120 days
Intervention Type
Drug
Intervention Name(s)
GAD-Alum
Other Intervention Name(s)
Diamyd
Intervention Type
Drug
Intervention Name(s)
Vitamin D
Other Intervention Name(s)
Calciferol
Primary Outcome Measure Information:
Title
Number of Subjects With Injection Site Reactions Month 1
Description
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Time Frame
Month 1
Title
Number of Subjects With Injection Site Reactions Month 2
Description
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Time Frame
Month 2
Title
Number of Subjects With Injection Site Reactions Month 3
Description
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Time Frame
Month 3
Title
Number of Subjects With Injection Site Reactions Month 32
Description
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Time Frame
Month 32, extension period
Secondary Outcome Measure Information:
Title
Mean Change in C-peptide AUC (Area Under the Curve) (Mean 120min) Value, Month 15
Description
Change from baseline to month 15 in C-peptide AUC (Area Under the Curve) (mean 120min) value AUC (mean 120min) (nmol/L) is the C-peptide AUC during an MMTT (nmol/L*minutes) divided by the duration of the MMTT (minutes) i.e. C-peptide weighted average concentration
Time Frame
Baseline to month 15 at 0, 30, 60, 90, 120 minutes post-dose
Title
Mean Change in C-peptide AUC(Mean 120min) Value, Month 30
Description
Change from baseline to month 30 in C-peptide AUC(mean 120min) value AUC (mean 120min) (nmol/L) is the C-peptide AUC during an MMTT (nmol/L*minutes) divided by the duration of the MMTT (minutes) i.e. C-peptide weighted average concentration
Time Frame
Baseline to month 30 at 0, 30, 60, 90, 120 minutes post-dose
Title
Mean Change in C-peptide AUC(Mean 120min) Value, Month 43
Description
Change from baseline to month 43 in C-peptide AUC(mean 120min) value AUC (mean 120min) (nmol/L) is the C-peptide AUC during an MMTT (nmol/L*minutes) divided by the duration of the MMTT (minutes) i.e. C-peptide weighted average concentration
Time Frame
Baseline to month 43, extension period at 0, 30, 60, 90, 120 minutes post-dose
Title
Mean Change in C-peptide 90-minute Value, Month 15
Description
Change from baseline to month 15 in C-peptide 90-minute value
Time Frame
Baseline to month 15
Title
Mean Change in C-peptide 90-minute Value, Month 30
Description
Change from baseline to month 30 in C-peptide 90-minute value
Time Frame
Baseline to month 30
Title
Mean Change in C-peptide 90-minute Value, Month 43
Description
Change from baseline to month 43 in C-peptide 90-minute value
Time Frame
Baseline to month 43, extension period
Title
Mean Change in Fasting C-peptide Value, Month 15
Description
Change from baseline to month 15 in fasting C-peptide value
Time Frame
Baseline to month 15
Title
Mean Change in Fasting C-peptide Value, Month 30
Description
Change from baseline to month 30 in fasting C-peptide value
Time Frame
Baseline to month 30
Title
Mean Change in Fasting C-peptide Value, Month 43
Description
Change from baseline to month 43 in fasting C-peptide value
Time Frame
Baseline to month 43, extension period
Title
Mean Change in HbA1c, Month 15
Description
Change from baseline to month 15 in HbA1c
Time Frame
Baseline to month 15
Title
Mean Change in HbA1c, Month 30
Description
Change from baseline to month 30 in HbA1c
Time Frame
Baseline to month 30
Title
Mean Change in HbA1c, Month 43
Description
Change from baseline to month 43 in HbA1c
Time Frame
Baseline to month 43, extension period
Title
External Insulin Dose, Baseline
Description
External insulin dose at baseline
Time Frame
Baseline
Title
External Insulin Dose, Month 15
Description
External insulin dose at month 15
Time Frame
Month 15
Title
External Insulin Dose, Month 30
Description
External insulin dose at month 30
Time Frame
Month 30
Title
External Insulin Dose, Month 43
Description
External insulin dose at month 43
Time Frame
Month 43, extension period
Title
Mean IDAA1c Values, Baseline
Description
Insulin dose-adjusted HbA1c (IDAA1c)
Time Frame
Baseline
Title
Mean IDAA1c Values, Month 15
Description
Insulin dose-adjusted HbA1c (IDAA1c)
Time Frame
Month 15
Title
Mean IDAA1c Values, Month 30
Description
Insulin dose-adjusted HbA1c (IDAA1c)
Time Frame
Month 30
Title
Mean IDAA1c Values, Month 43
Description
Insulin dose-adjusted HbA1c (IDAA1c)
Time Frame
Month 43, extension period

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Informed consent given by patients Type 1 diabetes according to the ADA (American Diabetes Association) classification with < 6 months diabetes duration Age 12.00-29.99 years at diagnosis of Type 1 diabetes Fasting C-peptide ≥0.12 nmol/L Pos GADA(Antibodies to GAD with molecular mass 65,000) but < 50 000 random units Females must agree to avoid pregnancy and have a negative urine pregnancy test Patients of childbearing potential must agree to using adequate contraception, until 1 year after the last administration of GAD-Alum. Exclusion Criteria: Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted) Continuous treatment with any inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted) Treatment with any oral or injected anti-diabetic medications other than insulin Treatment with Vitamin D, marketed or not, or unwilling to abstain from such medication during the trial A history of anaemia or significantly abnormal haematology results at screening A history of epilepsy, head trauma or cerebro-vascular accident, or clinical features of continuous motor unit activity in proximal muscles Clinically significant history of acute reaction to vaccines or other drugs in the past Treatment with any vaccine, including influenza vaccine, within 4 months prior to planned first study drug dose or planned treatment with any vaccine up to 4 months after the last injection with study drug. Participation in other clinical trials with a new chemical entity within the previous 3 months Inability or unwillingness to comply with the provisions of this protocol A history of alcohol or drug abuse A significant illness other than diabetes within 2 weeks prior to first dosing Known human immunodeficiency virus (HIV) or hepatitis Females who are lactating or pregnant (the possibility of pregnancy must be excluded by urine βHCG (beta-human chorionic gonadotropin) on-site within 24 hours prior to the GAD-Alum treatment) Males or females not willing to use adequate contraception until 1 year after the last GAD-Alum treatment Presence of associated serious disease or condition, including active skin infections that preclude subcutaneous injection, which in the opinion of the investigator makes the patient non-eligible for the study Deemed by the investigator not being able to follow instructions and/or follow the study protocol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johnny Ludvigsson, Professor
Organizational Affiliation
Linkoeping University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Linköping University
City
Linköping
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
33162978
Citation
Casas R, Dietrich F, Barcenilla H, Tavira B, Wahlberg J, Achenbach P, Ludvigsson J. Glutamic Acid Decarboxylase Injection Into Lymph Nodes: Beta Cell Function and Immune Responses in Recent Onset Type 1 Diabetes Patients. Front Immunol. 2020 Oct 9;11:564921. doi: 10.3389/fimmu.2020.564921. eCollection 2020.
Results Reference
derived
PubMed Identifier
30009185
Citation
Tavira B, Barcenilla H, Wahlberg J, Achenbach P, Ludvigsson J, Casas R. Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 Diabetes. J Diabetes Res. 2018 May 24;2018:9391845. doi: 10.1155/2018/9391845. eCollection 2018.
Results Reference
derived

Learn more about this trial

GAD-Alum (Diamyd) Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes (DIAGNODE-1)

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